Banting 1.
Published on 17/04/2023
Martin Missbach, who can look back on more than 30 years in medical drug research, not only witnessed the development firsthand of some of the industry’s most successful medicines. The 60-year-old scientist also saw the advent of breakthrough technologies and innovative work models which have helped speed up drug discovery during his long career.
Overseeing the efforts to create state-of-the-art research labs in the newly refurbished high-rise research facility Banting 1 on the Novartis Campus in Basel today, Missbach is optimistic that drug research will accelerate in the years to come as increased digitalization, coupled with intensive collaboration and state-of-the-art technology, is set to yield strong results.
His bullishness is rooted in a strong legacy. Novartis, which in the past few years has brought 12 new molecular entities to the market – a record in the pharmaceutical industry – not only has the technological power to do so, Missbach says. The company also has the right collaborative mindset to spur breakthrough innovation.
Missbach’s own scientific journey started in his childhood. “Even as a kid, the nicest thing for me was to spend free afternoons outside,” he says. “I was never someone to sit at home just reading books. The best thing for me was to be out in the countryside, be it in the forest or in the water, wherever. I always felt a deep connection to nature and to wildlife. To this day, in my spare time, I love to pursue my passion of nature and wildlife photography.”
The early fascination with nature brought him to the Swiss Federal Institute of Technology, where he soon found his primary passion: medicinal chemistry. “My awakening, so to speak, came when I was attending organic chemistry lectures as a student. I was immediately drawn to the fact that, with chemistry, you can create new molecules and learn how these interact with the biological universe.”
The charm of chemistry deepened with the years, especially when he worked on his master’s and Ph.D. theses in Zurich. To work on something “with an impact and meaning for patients,” later prompted him to shy away from an academic career in favor of joining the pharmaceuticals industry, a path he has never since regretted.
Missbach joined Ciba-Geigy in the early 1990s. There he would soon experience firsthand what molecules could do for patients as he had the chance to collaborate with, among many others, Peter Buehlmayer and Juerg Zimmermann, the inventors of Diovan® and Glivec®, two of the most successful Novartis drugs.
Missbach puts the success of the two drugs also down to the company’s work setup. “When I arrived at Ciba-Geigy in the early 1990s, this was an exciting time, as the company was about to change its lab and work culture,” Missbach remembers. “In one of the most modern buildings at that time, the chemistry labs were shared by two scientific teams, thus helping to increase communication and interaction between scientists.”
In the pre-computer era, scientists would generally work on their own projects or scaffolds and rarely share their new ideas with colleagues. But as technology advanced, and computers allowed for seamless communication, collaboration became increasingly important.
“This has really changed since I started my career in industry,” Missbach says. “In the past, scientists would work together, of course. But the extent to which scientific results and insights were shared was much less. In today’s environment, in which we can receive real-time information and share this across the globe, that kind of mindset is almost unthinkable.”
This is especially true in Banting 1, where various teams from diverse chemical disciplines now all work together in a single building. “In the past, we were dispersed across the Campus as well as in Klybeck. By bringing the teams now under one roof, we can take collaboration to the next level.”
With the promise of more intensive interaction between scientists from diverse research areas, Missbach is convinced that innovation is set to accelerate and that, most of all, patients will benefit from this in the long term.
Martin Missbach, for the past two years you have been working on co-locating various teams into the refurbished building Banting 1. How did you experience this period?
It was both a fascinating and a difficult project at the same time. When we met the architects in the spring of 2020 for the kick-off to retrofit the old WSJ-88 lab building with its tangled structure and create a new hub for the Global Discovery Chemistry group, the coronavirus pandemic hit, and we were in lockdown a week later. This put a lot of strain on work conditions. But I’m extremely happy that we were able to finish the building almost on time and start working here together.
Co-location is the magic word when it comes to Banting 1. In some ways, the building is like a miniature Campus spread over 10 floors. Can you describe what is happening inside the building?
The building houses around 230 scientists from diverse fields such as classical medicinal chemistry, analytical chemistry, specialized synthetic technologies and computer-based chemistry. Furthermore, we have installed a state-of-the-art pilot plant in the natural products arena to produce novel molecules as well as key enzymes with the aid of microorganisms. And what makes Banting 1 so special for the medicinal chemists is the fact that scientists collaborating with different disease areas who worked in separate corners of the Campus in the past are now in one building and can interact with each other and learn from each other.
How is this interaction going to happen?
We have taken the watercooler concept to a new level. For this reason, we have installed coffee areas only on every second floor to enhance the probability that people have chance meetings and get to know each other better. The meeting room areas are arranged in a similar way. To be honest, I’ve never seen so many colleagues per day in my 30-year career at Novartis. The building’s structure is already doing the trick.
Do you expect this form of interaction to spur innovation?
This was the whole idea of the Campus. To enhance communication and bring people from diverse fields of science together. If you look at the scientific innovations that have resulted from this concept over the past few years, I expect the setup of Banting 1 to help accelerate this trend. By the way, there are different ways of doing co-location. In Banting 1, we co-located the various disciplines of chemistry, in WSJ-386, in Fab-16 and Virchow-16 we have co-located medicinal chemistry with our partners in disease areas and functional areas like oncology, musculoskeletal diseases and chemical biology and therapeutics to enhance drug discovery through collaboration.
Can you provide an example?
Take our natural products pilot plant. Here we are working intensively with colleagues from other departments like chemical and analytical development to help produce clinical candidates at large scale using tailor-made enzymes that allow to run a reaction step in water at room temperature without large amounts of organic solvents. This is part of a company-wide effort in novel production methods that could one day change the way we produce medicines on a large scale.
Are there other highlights?
Yes. We’ve also created a lab-to-lab and building-to-building concept to analyze test samples directly out of the laboratory. In the past, researchers had to transfer test vials manually or by internal post. Now, our new tubular system allows this process to be automated and to get the results much faster, while optimizing the use of our analytical machines.
Can you talk about some of the key projects on which researchers are working in Banting 1?
Our scientists are working on several important NIBR-wide efforts. One key project, for example, is to identify molecules that bind in a covalent way. The hope is to create medicines that have a much longer target occupancy and can thus be more efficient.
Are there other examples?
Another company-wide effort is to create molecules that can help degrade disease-causing proteins. This is really a novel way of targeting difficult-to-treat diseases. Also, it’s another clear indication that small-molecule research has a viable future, as these molecules if well designed can act with very high efficiency.
Medicinal chemistry has been responsible for some of the biggest breakthroughs in the company’s history. Now, with the advent of new technologies, such as gene therapy or nuclear medicine, what is the future of small-molecule drug research?
The potential of small-molecule research is far from exhausted. Of course, new technologies have emerged over the past few decades, which have shown strong medical efficacy in a variety of disease areas. But as I said before, new approaches such as covalency, targeted protein degradation, ADCs (antibody-drug conjugates, RLT (radioligand therapy) or modalities that interfere with RNA are opening up new avenues for small-molecule research. On top of that, small molecules can act intracellularly, can penetrate into desired tissues like for example the brain. What you need is a clear strategy where to play and how to play.
Can you be specific?
We follow a best-in-class or first-in-class approach. Either we aim to develop molecules that no one has ever managed to produce before, or we try to create molecules with the highest possible efficacy. In both cases, we have proven that we can achieve this. Of course, failures are part and parcel of our trade, but I believe we have the manpower and the technological savviness to be successful.
You have witnessed the rise of breakthrough therapies such as Diovan and Glivec, as you worked closely with or knew the teams and researchers who worked on these drugs. Can you talk a little bit about what you think is the secret of scientific research?
To have had the chance to meet and work with these scientists, who have made such important contributions to the company, is, of course, an honor. But it is also clear that their success was not a one-way street. I still remember that doubts persisted over a long time over the viability of these compounds and even when they were launched, not everyone was convinced that these medicines would have a great impact. Of course, today, we know, with the benefit of hindsight. The secret in my view is to be persistent in pursuing an idea at the right time and to let go an idea at the right time, and finally to have good judgment when to choose which path.
What have you learned from these experiences?
What is often underestimated is the real complexity of drug research. While we can often easily find molecules that have a specific activity, the real trick is to design the molecule in such a way that it can survive the entire human environment and only act in its intended way. This requires a very holistic approach in which you are forced to constantly learn. Having said this, it is clear that no one has a magic cauldron and is able to design a drug for success without overcoming major hurdles. But the good news is that science is getting stronger.
Can you be specific?
Science is making progress on many fronts. With the cryo-electron microscope, for example, we can freeze proteins and study their molecular interaction on a level and scale that was impossible before. This opens up many avenues to better understand how our molecules interact with these proteins. So we can design them better and target proteins that, until now, were intangible for us. And new approaches in machine learning and artificial intelligence are likewise helping us to get a better sense of how we can design molecules and to choose which ones to make first.
Given the rising number of scientific possibilities, how do you choose between projects?
We still have so many ideas today. But we must become better at choosing the right ones. It’s not always easy to predict the outcome of a project. As I said before, you can hit a surprising roadblock because a molecule does not perform in the way you envisaged. You can then go on to investigate this problem. But the goal is to hit the right balance. Our goal is to develop drugs and not to do academic research. We should always keep this in mind when we decide whether to continue or discontinue a project.
Will collaboration help in this decision process?
Definitely. Experienced scientists are needed to make such judgment calls, which are never easy. As my experience with the Glivec and Diovan stories showed, such discussions can go in all directions. But a collaborative mindset is helpful. I am also convinced that collaboration, whether in Banting 1 or with our colleagues elsewhere on the Campus or in Cambridge, Emeryville or San Diego, will contribute to the Novartis pipeline in the years to come. We have outstanding talents and some of the best technology to make our work more efficient, faster and smarter, while at the same time allowing us to stay focused. This has been the case for the past 30 years, and I am convinced it will be in the future as well.
